This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tumor cells can be genetically changed to increase their ability to stimulate immunity. We have previously evaluated a Chronic Lymphocytic Leukemia (B-CLL), vaccine in a Phase I clinical trial where two immunity stimulating genes (called hCD40L and hIL-2) are placed into tumor cells and injected into patients with this disease. This vaccine produced a specific anti-tumor response without any significant side effects. However, the benefits were minor and short lived. To try and learn more about why this approach was not working long-term we looked at a type of tumor cell called the leukemic SP cells, and then a subsequent effect on the tumor as a whole, by prolonging the period of vaccination. HYPOTHESIS Prolonging the period of B-CLL vaccination will produce a longer term effect, decreasing tumor SP cells, thereby effecting the tumor a whole. SPECIFIC AIMS To determine the effects of prolonged immunization with CD40L expressing and IL2 secreting B-CLL cells on the Side Population (SP) of tumor cells, and on non-SP tumor cells. To determine whether MHC-restricted or unrestricted anti-tumor immune responses are induced and sustained by the prolonged immunization. To assess the safety of the prolonged vaccination schedule.